Different Blood Pressure Targets for Heart and Brain?

October 29, 2021

Blood pressure targets may need to be modified depending on the cardiovascular outcome for which the patient is most at risk, a new analysis of the ALLHAT trial suggests.

The results show that for a patient with a particular risk of stroke, more aggressive blood pressure lowering may be warranted than a patient with a particular risk for myocardial infarction (MI).

For the new analysis, the researchers used data from the landmark ALLHAT study of antihypertensive treatment to evaluate risk patterns for cardiovascular events and all-cause mortality associated with different systolic and diastolic blood pressure values simultaneously. They present their results as a "heat map" — a visual representation of where the lowest and highest risks are for any given systolic/diastolic combinations.

During a median follow-up of 4.4 years in the trial which included 33,357 participants, there were 2636 MIs, 866 heart failure events, 936 strokes, and 3700 deaths.

Results showed that for the composite outcome of all-cause mortality, MI, and heart failure, a U-shaped association was observed with both systolic and diastolic blood pressure, but the blood pressures associated with the lowest hazards differed for each outcome.

For example, a systolic/diastolic pressure of 140-155/70-80 mm Hg was associated with the lowest risk of all-cause mortality, compared with 110-120/85-90 mm Hg for MI and 125-135/70-75 mm Hg for heart failure. In contrast, the association of systolic and diastolic pressure and stroke was linear, with lower values of both measurements consistently linked to a lower risk of stroke.   

The new analysis was published in the October 26 issue of the Journal of the American College of Cardiology.

"Our paper shows that the optimal target blood pressure can also depend on which outcome we are most interested in — MI, heart failure, or stroke. How aggressive we want to be in lowering blood pressure could be influenced by whether a patient is more at risk of a future stroke or a cardiac event," senior author Tara Chang, MD, Stanford University, Palo Alto, California, told theheart.org | Medscape Cardiology.

"When we look at just cardiac events such as MI and heart failure, we see the traditional J-shaped curve with higher risks at both extremes. But we don't see that for stroke, where lower values are consistently better for both diastolic and systolic pressures," she added.  

"Our data strengthens the idea that 'one size fits all' for BP targets is probably not appropriate," Chang said.  

"We as clinicians already know that," she said. "We see patients every day where we take into account their age, comorbidities, and other medications when trying to find an optimal target for their blood pressure. But we are now suggesting that optimal blood pressure may also depend on the outcome of interest and may differ for patients at particular risk of stroke compared with those at particular risk of cardiac events."

Chang acknowledged that identifying patients more at risk of one type of cardiovascular event than another can be very challenging. 

"There is no simple calculator for trying to figure out whether a patient is more at risk of a stroke or a cardiac event, and a lot of the risk factors are the same. But if someone has a history of stroke, that make us focus more on stroke as a future event [that] we are particularly trying to prevent," she said. "And similarly, patients with a history of heart disease are probably at higher risk of a cardiac event. We have to use our clinical experience in this."

On advice for clinicians, she says: "Overall, we know blood pressure is suboptimal — half of patients do not even get to the most conservative targets. But when it comes to more specific targets, we can consider risk factors and what we know about the patient's history. It's all about individualization. The guidelines give us a ballpark, but the specific target has to be individualized for each patient. This is the art of medicine."

She added: "After looking at our data, some may say they would be a bit more aggressive in patients at particular risk of stroke, but I tend to start off with an aggressive target in all and then back off where appropriate."

The authors note that the current data alone cannot determine the optimal blood pressure targets for patients at this time, given that it is a retrospective observational analysis. Moreover, the achieved blood pressure associated with the lowest risk of the specified outcomes in the ALLHAT study may be dissimilar from blood pressure combinations reported in other studies and may have used different measurement methods.

They conclude that simultaneous consideration of systolic/diastolic pressures and the associated "heat map" of cardiovascular risk individualized to patient risk factors to guide clinical blood pressure management will need to be assessed in future prospective trials.

An "Uncomfortable Choice" for Physicians

In an accompanying editorial, Franz H. Messerli, MD, Swiss Cardiovascular, Bern, Switzerland, Evgeniya Shalaeva, MD, Tashkent Medical Academy, Uzbekistan, and Emrush Rexhaj, MD, University Hospital, Bern, Switzerland, say the most important finding in this analysis is that there was no J-shaped curve between stroke risk and systolic or diastolic blood pressure, with the association remaining linear down to a blood pressure level of 110/55 mm Hg.

"For stroke prevention, therefore, the old blood pressure adage 'the lower the better' holds true," they state.

"This is a pivotal take-home message for practicing cardiologists — were it not risky for the heart, the brain would prefer an optimally cerebroprotective systolic blood pressure of 110-120 mm Hg," the editorialists comment.

They point out that this fits in with the observation that because of autoregulation, the brain is able to maintain a relatively constant blood flow despite large fluctuations in perfusion pressure. But in contrast to the brain, perfusion of the heart predominantly occurs during diastole, so that an inappropriately low diastolic blood pressure is prone to compromise myocardial perfusion.

Messerli and colleagues note that these findings from the ALLHAT trial are consistent with observations in the 2003 INVEST study, in which there was a progressive preponderance of MI over strokes with low diastolic blood pressures among 22,576 participants with hypertension and coronary artery disease.

They report that in INVEST, the nadir of diastolic blood pressure for MI was 82.7 mm Hg, close to the ALLHAT value of 84 mm Hg.

They note that hypertension and coronary artery disease are the principal drivers of target organ heterogeneity and in both ALLHAT and INVEST patients had a high prevalence of coronary artery disease; unsurprisingly, in some younger, healthier populations— many with neither hypertension nor coronary artery disease — no target organ heterogeneity could be demonstrated after multiple adjustments.

The editorialists say the fact that two large prospective randomized hypertension trials have both shown target organ heterogeneity (with optimally protective blood pressure differing for the risk of stroke and the risk of MI) causes clinicians to face an uncomfortable choice of aiming to prevent cardiac events at the expense of cerebrovascular events or vice versa.

They give an example of a 76-year-old stable patient with coronary artery disease who recently had a transient ischemic attack and presents with a blood pressure of 148/68 mm Hg. To confer optimal cerebroprotection according to this latest ALLHAT analysis, systolic pressure should now be lowered by 28 mm Hg to below 120 mm Hg; however, because of stable coronary artery disease, the patient's diastolic should remain in the 80-mm Hg range, ie, to be increased by 16 mm Hg.  

"Obviously, a difficult endeavor, even for the most skilful clinician!" they point out.

The editorialists suggest that a possible solution to this situation is to attempt to mitigate one of the risk factors with revascularization, citing studies showing the J-shaped curve with lower diastolic blood pressures and MI only being present in nonrevascularized patients with coronary artery disease, whereas such a pattern no longer was evident after revascularization.

They note that this brings up a provocative question: When there is urgent need for low blood pressure in stable coronary artery disease patients because of cerebrovascular disease, should coronary arteries be revascularized prophylactically, even though this would go against the recent findings of the ISCHEMIA trial? This 2020 study suggested little benefit of revascularizing asymptomatic patients with stable coronary artery disease.

"Clearly this remains a complicated issue and it is unclear as to [whether] revascularization would improve tolerability of a lower diastolic blood pressure," the editorialists add.

They conclude that the blood pressure management of patients with both stable coronary artery disease and cerebrovascular disease remains challenging and needs careful shared decision-making. "Questions remain as to if we should continue with medical therapy aimed at lowering blood pressure, or should we consider further options for increasing diastolic pressure leeway, to the point of prophylactic coronary artery revascularization."

The authors and editorialists have disclosed no relevant financial relationships.

J Am Coll Cardiol. Published October 26, 2021. Abstract, Editorial

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